The objective of this line of research is to gain an understanding of relapse to tobacco dependence, and to develop treatments based on that understanding. Under current funding, we studied prevention of cessation- induced weight gain. After smoking treatment, subjects were randomly assigned to receive either innovative weight management, nonspecific treatment, or no treatment. Subjects assigned to the innovative condition gained less weight. At follow-ups assessments, however, smoking rates in subjects receiving the active treatments for weight gain were higher than those who received no weight treatment. This finding has important implications for the design of smoking treatment programs. We derived a quantitative indicator of current dysphoria at intake that predicted smoking treatment failure in a sample of 115 smokers. Also, we studied the effects of quitting smoking on 65 subjects with and without a Major Depressive Disorder History. History subjects entered treatment with more dysphoria than no history subjects and showed greater increases in negative moods while quitting. Final analyses are underway, including those correlating depressive history with smoking status. In an ongoing study, 123 subjects were assessed on depression history and were randomly assigned to either a mood management intervention plus 2 mg. nicotine gum or to low contact treatment plus 2 mg. nicotine gum. The hypothesis that smokers with a History of Major Depressive Disorder would be differentially aided in quitting by mood management was supported by preliminary results. We propose to continue our study of dysphoria, depression, and smoking treatment. In Experiment 1, subjects are assessed on Major Depressive Disorder, and randomly assigned to mood management or to a smoking treatment program that is equivalent in time, attention, and credibility, and to 2 mg. nicotine or 0.5 mg unbuffered placebo gum. Measures are taken at baseline and posttreatment, and at 12, 26, and 52 weeks after treatment termination. They include self-reported smoking, confirmatory biochemical measures, reports of significant others, and measures of mood, withdrawal symptoms, demoralization, drug and alcohol use, social support, and coping skills. In Experiment 2, following diagnostic assessment, subjects are randomly assigned to either an antidepressant, nortriptyline, or to placebo drug. Measures and time of assessment parallel those for Experiment 1. Nortriptyline blood levels are taken.